Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma
Tomasz P Radon, Nathalie J Massat, Richard Jones, Wasfi Alrawashdeh, Laurent Dumartin, Darren Ennis, Stephen W Duffy, Hemant M Kocher, Stephen P Pereira, Luisa Guarner posthumous, Cristiane Murta-Nascimento, Francisco X Real, Núria Malats, John Neoptolemos, Eithne Costello, William Greenhalf, Nick R Lemoine, Tatjana Crnogorac-Jurcevic, Tomasz P Radon, Nathalie J Massat, Richard Jones, Wasfi Alrawashdeh, Laurent Dumartin, Darren Ennis, Stephen W Duffy, Hemant M Kocher, Stephen P Pereira, Luisa Guarner posthumous, Cristiane Murta-Nascimento, Francisco X Real, Núria Malats, John Neoptolemos, Eithne Costello, William Greenhalf, Nick R Lemoine, Tatjana Crnogorac-Jurcevic
Abstract
Purpose: Noninvasive biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) are currently not available. Here, we aimed to identify a set of urine proteins able to distinguish patients with early-stage PDAC from healthy individuals.
Experimental design: Proteomes of 18 urine samples from healthy controls, chronic pancreatitis, and patients with PDAC (six/group) were assayed using GeLC/MS/MS analysis. The selected biomarkers were subsequently validated with ELISA assays using multiple logistic regression applied to a training dataset in a multicenter cohort comprising 488 urine samples.
Results: LYVE-1, REG1A, and TFF1 were selected as candidate biomarkers. When comparing PDAC (n = 192) with healthy (n = 87) urine specimens, the resulting areas under the receiver-operating characteristic curves (AUC) of the panel were 0.89 [95% confidence interval (CI), 0.84-0.94] in the training (70% of the data) and 0.92 (95% CI, 0.86-0.98) in the validation (30% of the data) datasets. When comparing PDAC stage I-II (n = 71) with healthy urine specimens, the panel achieved AUCs of 0.90 (95% CI, 0.84-0.96) and 0.93 (95% CI, 0.84-1.00) in the training and validation datasets, respectively. In PDAC stage I-II and healthy samples with matching plasma CA19.9, the panel achieved a higher AUC of 0.97 (95% CI, 0.94-0.99) than CA19.9 (AUC = 0.88; 95% CI, 0.81-0.95, P = 0.005). Adding plasma CA19.9 to the panel increased the AUC from 0.97 (95% CI, 0.94-0.99) to 0.99 (95% CI, 0.97-1.00, P = 0.04), but did not improve the comparison of stage I-IIA PDAC (n = 17) with healthy urine.
Conclusions: We have established a novel, three-protein biomarker panel that is able to detect patients with early-stage pancreatic cancer in urine specimens.
©2015 American Association for Cancer Research.
Figures
![Figure 1. Urine concentration of the candidate…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4539580/bin/emss-62963-f0001.jpg)
![Figure 2. Diagnostic performance of urine biomarkers…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4539580/bin/emss-62963-f0002.jpg)
![Figure 3. Urine concentration of the three…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4539580/bin/emss-62963-f0003.jpg)
Figure 4. Diagnostic performance of urine biomarkers…
Figure 4. Diagnostic performance of urine biomarkers in discriminating early pancreatic adenocarcinoma patients form healthy…
Figure 5. Exploratory comparison of plasma CA19.9…
Figure 5. Exploratory comparison of plasma CA19.9 and the urine biomarker panel in discriminating early…
![Figure 4. Diagnostic performance of urine biomarkers…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4539580/bin/emss-62963-f0004.jpg)
![Figure 5. Exploratory comparison of plasma CA19.9…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4539580/bin/emss-62963-f0005.jpg)
Source: PubMed